AGING AND CIRCADIAN CLOCK

Abstract Circadian rhythms are highly conserved, 24-hour, oscillations that tune physiology to the day/night cycle, enhancing fitness by ensuring that appropriate activities occur at biologically advantageous times. Disruption of proper circadian timing negatively impacts organismal fitness, making understanding the mechanism underlying circadian regulation over cellular physiology critical to appreciating a fundamental rule of life on earth. As we age, our bodies circadian rhythms change due to stress, chronic disruption of our clocks, neurodegeneration, and a host of other reasons, which can have a profound effect on our systems. Therefore, understanding the aging circadian clock is important to promote longevity and healthy aging. In this session, we will investigate some of the research going on that links the clock to aging. Topics will include the investigation of the role of the clock in timing immunometabolic regulation in the context of inflammation and Alzheimer’s disease, the optimization of the timing of exercise in the effort to maintain homeostasis and decrease risk, the connection between aging and the reduction of the number of rhythmically expressed genes and the weakening of circadian control, and the effect of dietary restriction on the circadian clock. The take home message of this session will be the importance of factoring daily time into research, preventative measures, and treatment regimens, to maximize overall health as we age.

Political participation encompasses institutionalised activities such as attending meetings of a political organisation as well as non-institutionalised activities including contacting politicians, signing petitions or boycotting.Both forms of activities tend to be dependent upon birth cohort, political socialisation, and period effects like changes in the welfare state design.Furthermore, it is also connected with other domains of civic engagement as well as trust.Social capital theory focuses on social connections and roles fostering civic engagement, including political participation, however, the relationship between social capital and political participation might look different for different types of political activities.The aim of this study was, therefore, to test the importance of social capital for different types of political participation in younger and older adults by analysing cross-national data from the European Quality of Life Survey (EQLS) in 2016.Data was collected in 33 European countries and includes more than 36,000 individuals aged 18 and over.Multilevel regression analysis was used to explore individual-level and country-level social capital on different measures of institutionalised and non-institutionalised political participation in younger and older adults.The results showed that a third of the sample participated in non-institutionalised activities whereas 11 percent participated in institutionalised activities.Both forms of political participation were lower among older adults as compared to younger age groups.While social capital was identified as an important predictor of political participation, it was also shown that these associations were conditioned by larger cultural, political and welfare institutional contexts.

CIVIC ENGAGEMENT AMONG OLDER MIGRANTS IN EUROPE: EXAMPLES FROM FOUR EUROPEAN COUNTRIES
Sandra Torres 1 , Pernilla Ågård 2 , Emilia Häkkinen 3 , Bas Dikmans 4 , Inma Peiro-Milan 5 , and Rodrigo Serrat 5 , 1. Uppsala University, Uppsala, Uppsala Lan, Sweden, 2. Uppsala University, Dept. of Sociology, Uppsala, Uppsala Lan, Sweden,3. Åbo Academy University,Vasa,Pohjanmaa,Finland,4. Vrije Universiteit Brussels,Brussels,Brussels Hoofdstedelijk Gewest,Belgium,5. University of Barcelona,Barcelona,Catalonia,Spain Scholarship on old age social exclusion has identified civic engagement as a research area that deserves empirical attention.Research on older people's civic engagement has in turn pointed out that experiencing life-course deficits in social capital, and/ or having had a life-course that does not resemble the continuity that social gerontology takes for granted, could put people at risk of becoming civically excluded in old age.These are two of the starting points for the European project known as CIVEX, which aims to study the life-course trajectories of civic engagement in groups of older people that have not yet received enough empirical attention.One of these groups is constituted by those who have migrated to the countries in which they are now based as adults, and whose life-course may therefore be more characterized by discontinuity rather than continuity.Departing from 60 life-course qualitative interviews with older migrants that are based in Sweden, Belgium, Spain and Finland, this presentation will draw attention to the ways in which these older people define civic engagement and the manner in which they describe how their migratory life-courses have impacted their civic engagement.The presentation will argue that there is theorizing potential embedded on the migratory life course, and that this could expand the scholarly imagination on old age social exclusion in general, and civic engagement in particular.
fitness by ensuring that appropriate activities occur at biologically advantageous times.Disruption of proper circadian timing negatively impacts organismal fitness, making understanding the mechanism underlying circadian regulation over cellular physiology critical to appreciating a fundamental rule of life on earth.As we age, our bodies circadian rhythms change due to stress, chronic disruption of our clocks, neurodegeneration, and a host of other reasons, which can have a profound effect on our systems.Therefore, understanding the aging circadian clock is important to promote longevity and healthy aging.In this session, we will investigate some of the research going on that links the clock to aging.Topics will include the investigation of the role of the clock in timing immunometabolic regulation in the context of inflammation and Alzheimer's disease, the optimization of the timing of exercise in the effort to maintain homeostasis and decrease risk, the connection between aging and the reduction of the number of rhythmically expressed genes and the weakening of circadian control, and the effect of dietary restriction on the circadian clock.The take home message of this session will be the importance of factoring daily time into research, preventative measures, and treatment regimens, to maximize overall health as we age.

CIRCADIAN TIMING OF THE IMMUNOMETABOLIC RESPONSE AFFECTS ALZHEIMER'S DISEASE PATHOLOGY Jennifer Hurley, Rensselaer Polytechnic Institute, Troy, New York, United States
Though the predominant model of the biological mechanisms underlying ADRDs is based on the beta-amyloid (Aβ) hypothesis, evidence suggests that inflammation from resident immune cells is also a key component of the development of ADRD pathophysiology.A major biological regulator of inflammation is the circadian clock, the 24-hour molecular timekeeper that broadly regulates gene expression throughout mammalian tissues to synchronize biology to the Earth's day/night cycle.Concordantly, chronic disruption of the circadian clock (CD) increases the risk for and severity of ADRDs.Our research has revealed that the circadian clock times metabolism, with the clock timing mitochondrial division which in turn times the response of mammalian macrophages to ADRD pathological factors.We show that subunits of the enzyme NOX2, a driver in the creation of reactive oxygen species (ROS) that uses metabolites to impart inflammation, are driven to oscillate in a 24 hr rhythm by the circadian clock in macrophages and microglia.Notably, oscillations in these NOX2 subunits are dysregulated when an organism undergoes CD, leading to an increase in the levels of ROS released by macrophages and microglia and elevating overall levels of inflammation.Given the apparent interconnection between inflammation, circadian rhythms, and ADRDs, an understanding of the circadian timing of the immune system could be exploited to develop treatments that alleviate ADRD symptoms, contribute to a potential cure, and prevent a population-wide increase in neurodegeneration due to a societal surge in CD.

AGE-ASSOCIATED DECLINE IN TISSUE CIRCADIAN CLOCK FUNCTION Karyn Esser, University of Florida, Gainesville, Florida, United States
Cellular circadian clocks direct a daily transcriptional program that supports homeostasis and resilience.Emerging evidence has demonstrated age-associated changes in circadian functions.To define age-dependent changes at the systems level, we profile the circadian transcriptome in the hypothalamus, lung, heart, kidney, skeletal muscle, and adrenal gland in three age groups.We find age-dependent and tissue-specific clock output changes but these changes exhibit tissue specific patterns.In general, aging reduces the number of rhythmically expressed genes (REGs), indicative of weakened circadian control.These REGs are enriched for the hallmarks of aging, adding another dimension to our understanding of aging.We determined there were tissue specific changes in the phase distribution of REGs with the hypothalamus and skeletal muscle tissues of the old mice showing a large reduction with REG peak expression at only one phase of the day.Analyzing all expressed genes within a tissue for differences at four distinct times of day identified unique clusters of differentially expressed genes (DEGs).These outcomes identify non-circadian but temporally distinct age associated changes in gene expression.This analysis extends the landscape for understanding aging and highlights the impact of aging on circadian clock function and temporal changes in gene expression.Many vital processes in the eye are under circadian regulation, and circadian dysfunction has emerged as a potential driver of eye aging.Dietary restriction (DR) is one of the most robust lifespan-extending therapies and amplifies circadian rhythms with age.We have previously shown that lifespan extension upon DR requires the presence of circadian clocks for maximal benefits.Herein, we demonstrate that dietary restriction extends lifespan in Drosophila melanogaster by promoting circadian homeostatic processes that protect the visual system from age-and light-associated damage.Altering the positive limb core molecular clock transcription factor, CLOCK, or CLOCK-output genes, accelerates visual senescence, induces a systemic immune response, and shortens lifespan.Flies subjected to dietary restriction are protected from the lifespan-shortening effects of photoreceptor activation.Inversely, photoreceptor inactivation, achieved via mutating rhodopsin or housing flies in constant darkness, primarily extends the lifespan of flies reared on a high-nutrient diet.Our findings establish the eye as a dietsensitive modulator of lifespan and indicates that vision is an antagonistically pleiotropic process that contributes to organismal aging.
Abstract citation ID: igad104.1680DIETARY RESTRICTION AND THE TRANSCRIPTION FACTOR CLOCK DELAY EYE AGING TO EXTEND LIFESPAN IN DROSOPHILA MELANOGASTER Pankaj Kapahi, Buck Institute for Research on Aging, Novato, California, United States